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Role of Intestinal Dysbiosis and Nutrition in Rheumatoid Arthritis

Attur, Malavikalakshmi; Scher, Jose U; Abramson, Steven B; Attur, Mukundan
Rheumatoid arthritis is a chronic systemic immune-mediated disease caused by genetic and environmental factors. It is often characterized by the generation of autoantibodies that lead to synovial inflammation and eventual multi-joint destruction. A growing number of studies have shown significant differences in the gut microbiota composition of rheumatoid arthritis (RA) patients compared to healthy controls. Environmental factors, and changes in diet and nutrition are thought to play a role in developing this dysbiosis. This review aims to summarize the current knowledge of intestinal dysbiosis, the role of nutritional factors, and its implications in the pathogenesis of rheumatoid arthritis and autoimmunity. The future direction focuses on developing microbiome manipulation therapeutics for RA disease management.
PMID: 35954278
ISSN: 2073-4409
CID: 5287212

Secukinumab in US Biologic-Naive Patients With Psoriatic Arthritis: Results From the Randomized, Placebo-Controlled CHOICE Study

Nguyen, Tien; Churchill, Melvin; Levin, Robert; Valenzuela, Guillermo; Merola, Joseph F; Ogdie, Alexis; Orbai, Ana-Maria; Scher, Jose U; Kavanaugh, Arthur; Kianifard, Farid; Rollins, Chauncy; Calheiros, Renato; Chambenoit, Olivier
OBJECTIVE:To evaluate secukinumab 300 mg and 150 mg vs placebo in a US-only population of biologic-naive patients with psoriatic arthritis (PsA). METHODS:CHOICE was a randomized, double-blind, controlled trial conducted in the United States. Biologic-naive patients with PsA and psoriasis were randomized 2:2:1 to secukinumab 300 mg (n = 103), secukinumab 150 mg (n = 103), or placebo (n = 52). The primary objective was to show superiority of secukinumab 300 mg vs placebo in ACR20 response at week 16. Additional objectives included the effect of secukinumab on dactylitis, enthesitis, psoriasis, and safety. RESULTS:= .0011). Secukinumab 300 mg also led to greater ACR50/70 responses and improvements in other variables vs placebo. Responses were generally sustained over time. Patients with inadequate response to secukinumab 150 mg at weeks 16, 28, or 40 who received dose escalation to 300 mg experienced improved clinical response after uptitration. The most common adverse events were upper respiratory tract infections and diarrhea. No inflammatory bowel disease was reported or new safety signals observed. CONCLUSION/CONCLUSIONS:Secukinumab 300 mg led to rapid and significant improvements over placebo in symptoms of PsA in this heavier population of US-only biologic-naive patients. Findings were consistent with previous studies and suggest that secukinumab 300 mg is a safe and efficacious first-line biologic treatment for patients with PsA.
PMID: 35428722
ISSN: 0315-162x
CID: 5219162

Response to: 'Microbiome in Sjögren's syndrome: here we are' by van der Meulen et al

Manasson, Julia; Blank, Rebecca B; Scher, Jose U
PMID: 32699036
ISSN: 1468-2060
CID: 4532502

GRAPPA 2020 Research Award Recipients

Castillo, Rochelle L; Yan, Di; Ashhurst, Anneliese S; Elliott, Ashley; Angioni, Maria Maddalena; Scher, Jose U; Naik, Shruti; Neimann, Andrea; Byrne, Scott N; Payne, Richard J; FitzGerald, Oliver; Pennington, Stephen R; Cauli, Alberto; Chandran, Vinod
At the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, a summary of the research conducted by the recipients of the 2020 GRAPPA Research Awards was presented by the awardees. The summary of the 4 presentations is provided here.
PMID: 35293338
ISSN: 0315-162x
CID: 5183902

A Randomized Open Label Clinical Trial of Lipid-Lowering Therapy in Psoriasis to Reduce Vascular Endothelial Inflammation

Garshick, Michael S; Drenkova, Kamelia; Barrett, Tessa J; Schlamp, Florencia; Fisher, Edward A; Katz, Stuart; Jelic, Sanja; Neimann, Andrea L; Scher, Jose U; Krueger, James; Berger, Jeffrey S
PMID: 34808233
ISSN: 1523-1747
CID: 5063372

Basic Science Session 2. Recent Advances in Our Understanding of Psoriatic Arthritis Pathogenesis

Lubberts, Erik; Scher, Jose U; FitzGerald, Oliver
The second basic science session at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting focused on 2 recent publications that have increased our understanding of the pathogenesis of psoriatic arthritis (PsA). Data from the first publication, presented by Prof. Erik Lubberts, showed that interleukin (IL)-17A is produced by CD4+ and not CD8+ T cells in PsA synovial fluid following T cell receptor activation. These findings contrast with previously published data, which had suggested that CD8+ T cells are a prominent source of IL-17A. In further experiments, they showed that when CD8+ T cells were stimulated with paramethoxyamphetamine/ionomycin, relatively high levels of IL-17A were detected. Prof. Jose Scher presented work on the role of the microbiome in PsA and more specifically, on pharmacomicrobiomics. He demonstrated the baseline collection of genomes and genes from the microbiota community (the metagenome) can be used as predictor for future treatment response in early rheumatoid arthritis and also likely in PsA.
PMID: 35169059
ISSN: 0315-162x
CID: 5175612

Psoriatic arthritis from a mechanistic perspective

Schett, Georg; Rahman, Proton; Ritchlin, Christopher; McInnes, Iain B; Elewaut, Dirk; Scher, Jose U
Psoriatic arthritis (PsA) is part of a group of closely related clinical phenotypes ('psoriatic disease') that is defined by shared molecular pathogenesis resulting in excessive, prolonged inflammation in the various tissues affected, such as the skin, the entheses or the joints. Psoriatic disease comprises a set of specific drivers that promote an aberrant immune response and the consequent development of chronic disease that necessitates therapeutic intervention. These drivers include genetic, biomechanical, metabolic and microbial factors that facilitate a robust and continuous mobilization, trafficking and homing of immune cells into the target tissues. The role of genetic variants involved in the immune response, the contribution of mechanical factors triggering an exaggerated inflammatory response (mechanoinflammation), the impact of adipose tissue and altered lipid metabolism and the influence of intestinal dysbiosis in the disease process are discussed. Furthermore, the role of key cytokines, such as IL-23, IL-17 and TNF, in orchestrating the various phases of the inflammatory disease process and as therapeutic targets in PsA is reviewed. Finally, the nature and the mechanisms of inflammatory tissue responses inherent to PsA are summarized.
PMID: 35513599
ISSN: 1759-4804
CID: 5216392

Methotrexate and TNF inhibitors affect long-term immunogenicity to COVID-19 vaccination in patients with immune-mediated inflammatory disease

Haberman, Rebecca H; Um, Seungha; Axelrad, Jordan E; Blank, Rebecca B; Uddin, Zakwan; Catron, Sydney; Neimann, Andrea L; Mulligan, Mark J; Herat, Ramin Sedaghat; Hong, Simon J; Chang, Shannon; Myrtaj, Arnold; Ghiasian, Ghoncheh; Izmirly, Peter M; Saxena, Amit; Solomon, Gary; Azar, Natalie; Samuels, Jonathan; Golden, Brian D; Rackoff, Paula; Adhikari, Samrachana; Hudesman, David P; Scher, Jose U
PMCID:8975261
PMID: 35403000
ISSN: 2665-9913
CID: 5218902

Proceedings of the 2021 GRAPPA-Collaborative Research Network (CRN) Meeting

Stober, Carmel; McInnes, Iain B; Raychaudhuri, Soumya; Mease, Philip J; Pennington, Stephen R; Scher, Jose U; Chandran, Vinod; Armstrong, April W; de Wit, Maarten; Cauli, Alberto; Jadon, Deepak R; Löve, Thorvardur J; Ogdie, Alexis; O'Sullivan, Denis; van Mens, Leonieke J J; Ritchlin, Christopher T; FitzGerald, Oliver
At the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)- Collaborative Research Network (CRN) annual meeting, the GRAPPA-CRN group presented a number of project updates, including a pilot investigator-initiated study to evaluate liquid and tissue biomarkers associated with axial involvement in psoriatic arthritis (PsA). The GRAPPA-CRN session updated progress made with 3 parallel international research initiatives based on 3 previously defined unmet needs in PsA. The Health Initiatives in Psoriasis and PsOriatic arthritis ConsoRTium European States (HIPPOCRATES) is a European research consortium formed to address unmet clinical needs in PsA. The Preventing Arthritis in a Multi-Center Psoriasis At-Risk Population (PAMPA) is a US-based organization that has defined consensus terminology for preclinical phases of PsA and is interested in the transition process from psoriasis to PsA. An overview of the Accelerating Medicines Partnership Autoimmune and Immune-Mediated Diseases (AMP AIM) program 2.0, a consortium including GRAPPA-CRN members that addressed these 3 unmet needs in PsA, was also presented.
PMID: 35365578
ISSN: 0315-162x
CID: 5220082

Evaluation of Immune Response and Disease Status in SLE Patients Following SARS-CoV-2 Vaccination

Izmirly, Peter M; Kim, Mimi Y; Samanovic, Marie; Fernandez-Ruiz, Ruth; Ohana, Sharon; Deonaraine, Kristina K; Engel, Alexis J; Masson, Mala; Xie, Xianhong; Cornelius, Amber R; Herati, Ramin S; Haberman, Rebecca H; Scher, Jose U; Guttmann, Allison; Blank, Rebecca B; Plotz, Benjamin; Haj-Ali, Mayce; Banbury, Brittany; Stream, Sara; Hasan, Ghadeer; Ho, Gary; Rackoff, Paula; Blazer, Ashira D; Tseng, Chung-E; Belmont, H Michael; Saxena, Amit; Mulligan, Mark J; Clancy, Robert M; Buyon, Jill P
OBJECTIVE:To evaluate seroreactivity and disease flares after COVID-19 vaccination in a multi-ethnic/racial cohort of patients with systemic lupus erythematosus (SLE). METHODS:90 SLE patients and 20 healthy controls receiving a complete COVID-19 vaccine regimen were included. IgG seroreactivity to the SARS-CoV-2 spike receptor-binding domain (RBD) and SARS-CoV-2 microneutralization were used to evaluate B cell responses; IFN-γ production to assess T cell responses was measured by ELISpot. Disease activity was measured by the hybrid SLE disease activity index (SLEDAI) and flares were assigned by the SELENA/SLEDAI flare index. RESULTS:Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS-CoV-2 spike RBD than controls. Twenty-six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti-dsDNA level prior to vaccination associated with decreased vaccine responses. IgG seroreactivity to the SARS-CoV-2 Spike RBD strongly correlated with the SARS-CoV-2 microneutralization titers and antigen-specific IFN-γ production determined by ELISpot. In a subset of patients with poor antibody responses, IFN-γ production was likewise diminished. Pre-/post-vaccination SLEDAI scores were similar. Only 11.4% of patients had a post-vaccination flare; 1.3% were severe. CONCLUSION/CONCLUSIONS:In a multi-ethnic/racial study of SLE patients 29% had a low response to the COVID-19 vaccine which was associated with being on immunosuppression. Reassuringly, disease flares were rare. While minimal protective levels remain unknown, these data suggest protocol development is needed to assess efficacy of booster vaccination.
PMCID:8426963
PMID: 34347939
ISSN: 2326-5205
CID: 5046532